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I Zamora

Publications and source records attributed to I Zamora.

At least 19 recordsLinked to original sources
PubMed2006

Renal donor implication in the origin of BK infection: analysis of genomic viral subtypes.

UNLABELLED: BK virus (BKV) reactivation in immunocompromised kidney transplant patients can produce a tubulointerstitial nephropathy (BKVN). Molecular tools that test for DNA-BKV provide early detection and assist in management, but some aspects of the pathogenesis of this infection, such as donor causality, remain unclear. MATERIALS AND METHODS: Between November 2004 and January 2006, 55 Spanish kidney donors were studied for BK infection. A quantitative PCR assay was performed on urine and serum to detect BKV. To determine the origin of the viral infection, a transcription control region of the BK polymorphism sequence was designed to identify the viral subtype. RESULTS: Fifteen of 55 (27%) donors were BK-PCR positive: 13 in urine and 2 in serum and urine. Moreover, monitoring of recipient pairs detected BK-PCR positivity in 14 of 73 recipients. We studied eight BK-PCR positive recipients (corresponding to four pairs) and their respective donors. The same viral genome was observed in the four pairs, namely, the A250-1-a, WW-like, AS, and JL genotypes. Interestingly, one of the four pairs showed the donor and the two recipients to display exactly the same JL genotype. CONCLUSION: On the basis of our preliminary results analyzing the molecular fingerprints of donor and recipient pairs, we have presented new data implicating the donor, in at least some cases, as the source of BK infection.

BK Virus↗
PubMed2005

Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome.

Attempts to minimize the effects of prolonged steroid use in steroid-dependent nephrotic syndrome (SDNS) and the need to overcome steroid resistance (SRNS) justifies immunosuppressant therapy. We report our experience in a cohort of patients with SD/SRNS during the administration of mycophenolate mofetil (MMF) in a prospective protocol initiated in January 2001. Twenty-six children with idiopathic nephrotic syndrome were included (21 steroid dependent and 5 steroid resistant), whose response did not change after sequential treatment with cyclophosphamide (CPM) and cyclosporine (CsA). Histopathologic patterns were: 11 minimal change disease (MCD), 1 diffuse mesangial proliferation (DMP), 13 focal segmental glomerulosclerosis (FSGS) and membranous 1 glomerulonephritis (MGN). The median age of onset of NS was 2.8 years (range 1.2-12.5), and treatment with MMF was performed at a median age of 11.4 years (range 5-17) with an initial dose of 600 mg/m(2)/12 h, adjusted to maintain levels of mycophenolic acid (MPA) at 2.5-5 mcg/ml. The planned duration of study to assess treatment efficacy was 6 months. The mean MMF dose required was 624 (SD=136) mg/m(2)/12 h (range 415-970), which maintained mean C(0)-MPA levels of 2.9 (SD=1.17) mcg/ml (range 1.2-5.9 mcg/ml). In the five patients with SRNS, only one achieved complete remission. In the patients with SDNS, steroid sparing was achieved in 15 and 9 remained in remission on MMF monotherapy. Withdrawal of MMF resulted in immediate relapse in 47%. In our study, MMF was a useful immunosuppressant due to its fewer undesirable effects and similar efficacy to other drugs used. It appears effective for the maintenance of remission in SDNS patients, with a response similar to that of CsA.

Child↗
PubMed2005

Polymerase chain reaction detection of BK virus and monitoring of BK nephropathy in renal transplant recipients at the University Hospital La Fe.

INTRODUCTION: Reactivation of BK infection occurs in immunocompromised hosts causing tubulointerstitial nephropathy (BKVN). Approximately 5% of kidney transplant recipients (KTR) develop BKVN, special half of whom lose their grafts. However, BKVN morphologic diagnosis on a renal biopsy is complicated, because the cytopathic changes can sometimes mimic rejection. Thus, BKV DNA-polymerase chain reaction (PCR) assay on serum, urine, and renal tissue is useful for early detection and monitoring of BKV. MATERIALS AND METHODS: We performed routine monthly urine cytologies looking for decoy cells as a marker of virus replication. Then, we performed a qualitative PCR on urine and serum in all recipients (independently of positive or negative cytology). We amplified 3 BK viral genome regions, LT (early transcription region) and VP1 (late transcription region) seeking a more accurate virus detection, and the TCR (control transcription region) region to perform a polymorphism sequence analysis to identify the BK genomic variant. Finally, the BKVN diagnosis was confirmed using renal biopsy. RESULTS: At present, 132 patients have been monitored. Thirteen of 40 (33%) were PCR-urine-positive cases (5 LT+/VP1- and 8 LT+/VP1+), and 10 of 132 (7.5%) were PCR-serum-positive cases (7 LT+/VP1- and 3 LT+/VP1+). When we compared PCR-urine and cytology results, 11 of 40 (27.5%) patients showed a positive cytology, 6 of whom were PCR- urine-positive (1 LT+/VP1- and 5 LT+/VP1+); whereas, 29 patients showed a negative cytology, 7 of whom were PCR-urine-positive(3 LT+/VP1- and 4 LT+/VP1+). Thus, comparison of PCR- urine and cytology results revealed false-positive and false-negative cases. Finally, TCR sequence analysis was performed in 9 patients to identify the BK genomic variants. CONCLUSION: Testing for BKV DNA in urine and serum is a noninvasive early detection assay and monitoring tool.

Adult↗
PubMed2005

Renal transplantation in children with severe bladder dysfunction.

PURPOSE: Renal transplantation in children with bladder dysfunction carries a risk for the renal graft. We report our experience with transplantation in 15 patients 6 to 18 years old with severe abnormalities of the lower urinary tract. MATERIALS AND METHODS: A total of 18 renal transplants were performed in 15 children with bladder dysfunction secondary to myelomeningocele (3), occult spina bifida (1), malformation/agenesis of the sacrum (5), posterior urethral valves (4), female hypospadias (1) and bladder exstrophy (1) between 1979 and 2003. Urological surgery was performed before transplantation in 14 cases-7 bladder augmentations, 5 incontinent urinary conduits/reservoirs and 2 vesicostomies. Voiding was maintained by intermittent catheterization in 9 cases and incontinent ostomies in 6. Graft implantation was performed by extraperitoneal route with ureteral anastomosis to the native bladder in cases of bladder augmentation. Immunosuppression consisted of triple therapy with polyclonal/monoclonal antibodies. RESULTS: Urological complications consisted of urethral obstruction due to mucus hypersecretion (1), urinary fistula (1), ureterovesical obstruction (1), stone formation (3), urinary tract incrustation by Corynebacterium urealyticum (1) and pyelonephritis (2). Graft survival rates at 1 and 5 years were 77% and 62%, respectively, with a median of 79 months (95% CI 51 to 107). Three graft losses were related to urological disease. CONCLUSIONS: Renal transplantation in children with severe bladder dysfunction can achieve similar results to those obtained in the general population. Meticulous selection of patients and surgical reparative techniques ensuring voiding and adequate control of urinary infections are mandatory. Augmentation cystoplasty and intermittent catheterization are appropriate techniques currently used for achieving this outcome.

Adolescent↗
PubMed2004

[Mesangial glomerulonephritis and intermediate uveitis].

Uveitis in children are less frequent than in adults. Their prognosis is variable because it may be found as an isolated and idiophatic condition or in association with definite clinical entities. The associated noninfectious diseases with predominantly renal involvement are tubulointerstitial nephritis and uveitis syndrome (TINU syndrome), mesangial glomerulonephritis isolated or in association with Behçet's disease. A case of 14-years-old girl with intermediate uveitis (pars planitis) and mesangial glomerulonephritis is presented. The ocular symptoms was eye redness and ocular pain and she has snow-banks in pars plana. She showed microscopic hematuria and intermitent proteinuria that increased during the ocular clinical exacerbation. Renal biopsy revealed both mild mesangial matrix increase and mesangial celullarity with normal tubulointerstitial structure and mesangial deposition of IgA and IgG immunoglobulins. This case is de first pediatric patient report in the literature with intermediate uveitis and mesangial glomerulonephritis with immune deposition. Mesangial glomerulonephritis were observed in patients whit Behçet disease, known etiological cause of uveitis in adults and children. These findings may suggest that uveitis and glomerulonephritis have common immunological pathogenesis including circulatory immune complexes. In uveitis patients, screening for associated extra-ocular and renal manifestations is mandatory and should have careful long-term follow-up with regular systemic evaluation.

Adolescent↗
PubMed2002

[Anti-CD25 monoclonal antibody against polyclonal antibodies in pediatric renal transplantation].

UNLABELLED: Although usually reversible, acute rejection of kidney graft is a negative factor in long-term graft survival. Commonly used in pediatric renal transplantation, immunosuppresive induction therapy is established to prevent it. New immunosuppressive agents have been developed in recent years and among them anti-CD25 monoclonal antibody appears to be specially interesting. AIM: To evaluate efficacy and safety of anti-CD325 monoclonal antibody (basiliximab) versus polyclonal antibodies as induction therapy in renal transplantation. MATERIAL AND METHODS: Thirty consecutive kidney transplants performed in children 4-16 years age in Hospital Infantil La Fe through 1997-2000. The first 15 patients received polyclonal antibodies as induction therapy, and 15 consecutive ones received monoclonal anti-CD25 antibodies. Receptor, donor and graft characteristics were similar in both groups. Also, maintenance immunosuppression was the same. RESULTS: The follow-up was over one year in all patients. Four patients in the polyclonal antibody group suffered one acute rejection episode and four other patients had some drug reaction. In the anti-CD25 treatment group there was one episode of acute graft rejection and no collateral effects were observed. Glomerular filtration rate, proteinuria, hypertension, infection episodes, graft and patient survival were similar in both groups. CONCLUSIONS: Induction therapy for pediatric renal transplantation with anti-CD25 antibody has been effective and safe. Compared with polyclonal antibodies as standard treatment, basiliximab reduced acute rejection episodes and had no collateral side effects. Graft and patient one year survival were identical in the two groups.

Adolescent↗
PubMed2001

Analysis of selective regions in the active sites of human cytochromes P450, 2C8, 2C9, 2C18, and 2C19 homology models using GRID/CPCA.

This study demonstrates a selectivity analysis using the GRID/CPCA strategy on four human cytochrome P450 2C homology models (CYP2C8, 2C9, 2C18, and 2C19). Although the four enzymes share more than 80% amino acid sequence identity, the substrate specificity differs. To investigate the selectivity of the enzymes and the amino acids that determine the specificity of each CYP2C enzyme, a selectivity analysis was made using GRID/CPCA. In the GRID calculations 10 probes were used covering hydrophobic, steric, and hydrogen bond acceptor and donor interactions. The selectivity analysis showed that the most important determinants of selectivity among the CYP2C models are the geometrical features of the active sites and the hydrophobic interactions. The selectivity analysis singled out CYP2C8 as the most different of the four CYP2C enzymes with amino acids with distinct properties in positions 114, 205, and 476 (Ser, Phe, and Ile, respectively) compared to the other enzymes. An inverse pharmacophore model for CYP2C9 was constructed from the selective regions, and the model agreed with the docking of diclofenac where the properties of the ligand overlapped with the pharmacophoric points in the model.

Amino Acid Sequence↗
PubMed2001

Competitive CYP2C9 inhibitors: enzyme inhibition studies, protein homology modeling, and three-dimensional quantitative structure-activity relationship analysis.

This study describes the generation of a three-dimensional quantitative structure activity relationship (3D-QSAR) model for 29 structurally diverse, competitive CYP2C9 inhibitors defined experimentally from an initial data set of 73 compounds. In parallel, a homology model for CYP2C9 using the rabbit CYP2C5 coordinates was built. For molecules with a known interaction mode with CYP2C9, this homology model, in combination with the docking program GOLD, was used to select conformers to use in the 3D-QSAR analysis. The remaining molecules were docked, and the GRID interaction energies for all conformers proposed by GOLD were calculated. This was followed by a principal component analysis (PCA) of the GRID energies for all conformers of all compounds. Based on the similarity in the PCA plot to the inhibitors with a known interaction mode, the conformer to be used in the 3D-QSAR analysis was selected. The compounds were randomly divided into two groups, the training data set (n = 21) to build the model and the external validation set (n = 8). The PLS (partial least-squares) analysis of the interaction energies against the K(i) values generated a model with r(2) = 0.947 and a cross-validation of q(2) = 0.730. The model was able to predict the entire external data set within 0.5 log units of the experimental K(i) values. The amino acids in the active site showed complementary features to the grid interaction energies in the 3D-QSAR model and were also in agreement with mutagenesis studies.

Animals↗
PubMed1997

Synthesis and molecular modeling: related approaches to progress in brassinosteroid research.

In the field of brassinosteroids, which are potent plant growth regulators, we have developed a quantitative structure-activity relationship study to develop knowledge from a structural point of view and to find out new requirement definitions. This will help identify other suitable active brassinosteroid derivatives with a good activity/synthetic cost ratio for further application in agriculture. The methodology used to achieve this goal represents a multidisciplinary study involving synthesis, molecular modeling calculations, and bioactivity evaluation. The influence of different molecular properties in the bioactivity of a set of synthetic compounds (i.e., molecular electrostatic potential and the ability to form H bonds) is discussed. The molecular electrostatic potential is expressed in terms of the electrostatic Carbó similarity index (CI) between brassinolide (1) and other brassinosteroids. We have found that the electrostatic charges of the functional groups play an important role in the description of the activity, as evidenced by its good correlation with the CI in most cases. Deviation from this rule could be explained by the H bonding abilities of some of these compounds, which we believe may play an essential role in binding to the natural receptors.

Brassinosteroids↗
PubMed1994

Attenuated varicella virus vaccine in children with renal transplants.

The long-term efficacy of varicella vaccine was studied in 34 children aged 2-18 years who were either on chronic dialysis (n = 17) or were renal transplant recipients (n = 17). Live attenuated virus (OKA line) was inoculated in a single 0.5-ml subcutaneous dose, without modification of the immunosuppressive therapy protocol for renal transplant recipients. The majority of children (85%) developed antibodies within the first 6 months, with IgG titres (enzyme-linked immunosorbent assay) greater than 1:40 (geometric mean 1:640). Of those children who were followed for longer than 2 years, 76% maintained their antibody titres. Reactions to the vaccine were minimal and the immunological protection was effective. Only 3 children developed a mild form of varicella in the post-vaccination period. We consider that seronegative children who are candidates for renal transplantation must be protected against varicella by attenuated varicella vaccination. When vaccination is performed after transplantation, no modification of immunosuppressive therapy is needed.

Adolescent↗
PubMed1984

Shunt nephritis: a report on five children.

Of 5 children with glomerulonephritis with infected ventriculoatrial shunt, 3 had improved renal function after antibiotic therapy and removal of the infected shunt. 1 patient with endoextracapillary proliferative glomerulonephritis with 70% glomerular crescents developed a rapidly progressive renal insufficiency. Renal failure was successfully managed by hemodialysis and kidney transplantation. 1 patient died from extrarenal causes in the course of a septic episode.

Acute Kidney Injury↗
PubMed1982

[Shunt nephritis (author's transl)].

Five patients aged 1.1 - 4.3 years, affected by nephritis secondary to infection of ventriculo-atrial shunt are presented. The time lag between the occurrence of shunt infection and diagnosis of nephropathy varied from 1 to 12 months. In four patients "Staphylococcus epidermidis" was isolated from blood and CSF cultures, and "Staphylococcus aureus" in another one. Renal lesion presented as hematuria and proteinuria, and two patients developed a nephrotic syndrome. Hypertension was present in three patients. C'2 and D'4 hypocomplementemia was a constant feature in the acute stage of the disease. Endocapillary glomerulonephritis was observed in three patients and endo-extracapillary glomerulonephritis in one (70% of crescent formations). After shunt removal and antibiotic administration a favorable clinical course was followed in three patients, with remission of nephropathy signs. The fifth patient (non biopsied) died in the course of a septic process, having kept until then a good renal function.

Cerebrospinal Fluid Shunts↗